Desulfurative Functionalization of ß-Acyl Allylic Sulfides with N-H Free Indoles Highly Regioselective at C3 and N1 Positions: Rapid Access to α-Branched Enones.

A regiodivergent allylation of 1H-indoles highly selectively at the C3 and N1 positions with ß-acyl allylic sulfides through desulfurative C-C/C-N bond-forming reactions has been developed under mild conditions. Notably, the remarkable site-selective switch can be achieved by a delicate choice of solvents and bases. This cost-efficient method displays a broad substrate scope, good functional compatibility, and excellent site-selectivity, thus offering a divergent synthesis of indole substituted α-branched enones, which possess diverse potential opportunities for further applications and derivatization.

Palladium-Catalyzed Regioselective Coupling Cyclohexenone into Indoles: Atom-Economic Synthesis of ß-Indolyl Cyclohexenones and Derivatization Applications.

Herein, we report a palladium-catalyzed dehydrogenative cross-coupling of indoles with cyclic enones to give ß-indolyl cyclic enones under mild and neutral reaction conditions. The key to the success is to explore a mild condition, which ensures the indole C-H activation and subsequent syn ß-hydride elimination through rapid enolization isomerization of Pd(II)-enolate while suppressing other undesired side reactions. Synthetic utility has also been demonstrated in the flexible transformation of the coupling products to meta-phenols and benzo[a]carbazoles.

Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial

BackgroundSARS-CoV-2 is a novel human coronavirus, there is no specific antiviral drugs. It has been proved that host-cell-expressed CD147 could bind spike protein of SARS-CoV-2 and involve in host cell invasion. Antibody against CD147 could block the infection of SARS-CoV-2. We aimed to assess the efficacy and safety of meplazumab, a humanized anti-CD147 antibody, as add-on therapy in patients with COVID-19 pneumonia. MethodsAll patients received recommended strategy from Diagnosis and Treatment for 2019 Novel Coronavirus Diseases released by National Health Commission of China. Eligible patients were add-on administered 10 mg meplazumab intravenously at days 1, 2, and 5. Patients hospitalized in the same period were observed as concurrent control. The endpoints include virological clearance rate, case severity, chest radiographic, and laboratory test. This trial was approved by the Ethics Committee of Institution at the Tangdu hospital, and registered with ClinicalTrials.gov, NCT 04275245. Findings17 patients were enrolled and assigned to meplazumab group between Feb 3, 2020 and Feb 10, 2020. 11 hospitalized patients served as concurrent control. Baseline characteristics were generally balanced across two groups. Compared to control group, meplazumab treatment significantly improved the discharged (p=0.006) and case severity (p=0.021) in critical and severe patients. The time to virus negative in meplazumab group was reduced than that in control group (median 3, 95%CI[1.5-4.5] vs. 13, [6.5-19.5]; p=0.014, HR=0.37, 95%CI[0.155-0.833]). The percentages of patients recovered to the normal lymphocyte count and CRP concentration were also increased remarkably and rapidly in meplazumab group. No adverse effect was found in meplazumab-treated patients. InterpretationMeplazumab efficiently improved the recovery of patients with SARS-CoV-2 pneumonia with a favorable safety profile. Our results support to carry out a large-scale investigation of meplazumab as a treatment for COVID-19 pneumonia. FundingNational Science and Technology Major Project.

Palladium-Catalyzed Controllable Reductive/Oxidative Heck Coupling between Cyclic Enones and Thiophenes via C-H Activation.

Herein, we report a straightforward, environmentally friendly, and controllable palladium/ligand catalytic system to enable reductive/oxidative Heck reactions of cyclic enones with thiophene or furan derivatives via C-H activation. The key to this tunable reaction is the appropriate intercepting thienyl-Pd(II)-enolate during the enolization process. Such a controllable and economic protocol would not only provide efficient methods to construct various value-added ß-heteroarylated cyclic ketones/enones but also shed light on developing other conjugate addition reactions via C-H activation.

Palladium-catalyzed dehydrogenative coupling of cyclic enones with thiophenes: a rapid access to ß-heteroarylated cyclic enones.

Dehydrogenative coupling of cyclic enones with heteroarenes has been a longstanding challenge because of the competitive ketone dehydrogenation and conjugated addition. Herein, a dehydrogenative coupling reaction of cyclic enones of different sizes with substituted thiophenes to construct ß-thienyl cyclic enone compounds through palladium-catalyzed C-H functionalization under mild reaction conditions is reported. Simple substituted thiophenes with different functional groups can be directly introduced into cyclic enones with predominant regioselectivity at the α position of thiophene moieties and excellent functional group tolerance. Further molecular transformations of the coupling products to synthetically useful meta-heteroarylated phenol derivatives have also been demonstrated.

Acid Promoted Direct Cross-Coupling of Methyl Ketones with Dimethyl Sulfoxide: Access to Ketoallyl Methylsulfides and -sulfones.

A new strategy to prepare ß-acyl allylic methylsulfides and -sulfones through acid promoted direct cross-coupling of methyl ketones with dimethyl sulfoxide (DMSO) is reported. The reaction proceeded through the nucleophilic attack of enamine intermidiates derived from ketones to in situ generated thionium ion species, followed by elimination of methanthiol to give ketoallylic methylsulfides. With the prolonged reaction time, such products could be further reacted with a methyl sulfonyl radical, which might be generated from a methylthiosulfonate species, to afford ketoallylic methylsulfones in high yields. Molecular transformations of the allylic methylsulfides were also demonstrated.

Peg-IFNa-2a/RBV antiviral efficacy in cirrhotic hepatitis C patients after splenectomy or partial splenic embolization / 中华肝脏病杂志

To investigate the antiviral efficacy of combination therapy with pegylated-interferon alpha (peg-IFNa)-2a and ribavirin (RBV) in hepatitis C patients with liver cirrhosis after splenectomy or partial splenic embolization. Forty-nine hepatitis C patients with liver cirrhosis who were unable to use antiviral therapy because of hypersplenism were recruited for study and treated with splenectomy or partial splenic embolization. Three months later, a regimen of antiviral combination therapy was initiated with peg-IFNa-2a (once-weekly subcutaneous injection: 135 μg or 180 μg) and RBV (daily oral: 800 to 1200 mg), and was maintained for 48 weeks. The patients were followed up at treatment weeks 1, 2, 4, 6, 8, and 12. Thereafter, follow-up was conducted every four weeks. The patients were observed until 24 weeks after treatment discontinuation. Follow-up testing included liver function, blood chemistry, renal function, and HCV RNA level. Any adverse reactions were recorded. Liver cirrhosis patients complicated by hypersplenism can be treated effectively with peg-IFNa-2a/RBV combination antiviral therapy after splenectomy or partial splenic embolization. The antiviral-induced sustained viral response rates was 65.00% in cirrhotic/hypersplenic hepatitis C patients receiving splenectomy and 58.62% in those receiving partial splenic embolization. Hypersplenism patients with hepatitis C-related cirrhosis achieved a good antiviral therapeutic effect with peg-IFNa-2a/RBV combination therapy following splenectomy or partial splenic embolization. This sequence of treatment may help to decrease incidences of chronic hepatitis C-induced liver failure and liver cancer in these patients.

Study on virus-specific cytotoxic T-lymphocyte responses in Chinese human immunodeficiency virus type 1 infection / 中华传染病杂志

Objective To investigate the features of HIV-1-specific Cytotoxic T-Lymphocyte (CTL)responses in Chinese.Methods The HIV-1-specific CTL responses were analyzed in an IFN-?ELISPOT assay by using a matrix system containing 820 overlapping peptides spanning the entire HIV-1 Clade B and C consensus sequence.Results The HIV-1-specific CTL response almost clus- tered in Gag and Nef across either HIV-1 Clade B(HIV-1 B)or HIV-1 Clade C(HIV-1 C),while oth- er proteins could also be recognized at different level.In comparison of the response between HIV-1 Clade B and Clade C,the magnitude and frequency was roughly identical with some difference found at single-peptide level.The most frequently recognized peptides of HIV-1 B were located in Nef,GPKEP- FRDYVDRFYKTLR(5/17,29.4%)and Gag,LWVYHTQGYFPDWQNY(5/17,29.4%),while the most frequently recognized peptide of HIV-1 C was located in Gag GPKEPFRDYVDRFFKTLR(6/17, 35.29%).Conclusions HIV-1-specific CTL responses clustered within HIV-1 Gag and Nef in Chinese. However,there was some difference between HIV-1 B and HIV-1 C at single-peptide level.